Biomimetic Multifunctional Graphene-Based Coating for Thermal Management, Solar De-Icing, and Fire Safety: Inspired from the Antireflection Nanostructure of Compound Eyes.

Due to the ubiquitous and inexhaustible solar source, photothermal materials have gained considerable attention for their potential in heating and de-icing. Nevertheless, traditional photothermal materials, exemplified by graphene, frequently encounter challenges emanating from their elevated reflectance. Inspired by ocular structures, this study uses the Fresnel equation to enhance the photo-thermal conversion efficiency of graphene by introducing a polydimethylsiloxane (PDMS)/silicon dioxide (SiO2) coating, which reduces the light reflectance (≈20%) through destructive interference. The designed coating achieves an equilibrium temperature of ≈77 °C at one sun and a quick de-icing in ≈65 s, all with a thickness of 5 µm. Simulations demonstrate that applying this coating to high-rise buildings results in energy savings of ≈31% in winter heating. Furthermore, the combination of PDMS/SiO2 and graphene confers a notable enhancement in thermal stability through a synergistic flame-retardant mechanism, effectively safeguarding polyurethane against high temperatures and conflagrations, leading to marked reduction of 58% and 28% in heat release rate and total heat release. This innovative design enhances the photo-thermal conversion, de-icing function, and flame retardancy of graphene, thereby advancing its applications in outdoor equipment, high-rise buildings, and aerospace vessels.

Kidney Injury: Focus on Molecular Signaling Pathways.

Acute kidney injury (AKI) is a syndrome in which kidney function reduces suddenly. This syndrome which includes both structural changes and loss of function may lead to chronic kidney disease (CKD). Kidney regeneration capacity depends on the cell type and severity of the injury. However, novel studies indicated that regeneration mostly relies on endogenous tubular cells that survive after AKI. Regenerative pharmacology requires a great knowledge of fundamental processes involved in the development and endogenous regeneration, leading to a necessity for investigating related signaling molecules in this process. Regulatory non-coding RNAs (ncRNAs) including microRNAs (miRNAs), long non-coding RNAs (lncRNAs), and circular RNAs (circRNAs) are currently known as critical regulators of gene expression in various cellular processes, and this regulatory function is also observed in nephrotic tissue, following damaging insults, which may promote or inhibit the progression of damage. Thus, studying signaling molecules and pathways involved in renal injury and repair results in a comprehensive prospect of these processes. Moreover, these studies can lead to new opportunities for discovering and enhancing therapeutic approaches to renal diseases. Herein, we review studies dealing with the role of different signaling pathways involved in renal injury. Besides, we discuss how some signaling pathways are useful for the repair process following AKI.

Ag-Cu filled nanonets with ultrafine dual-nanozyme active units for neurotransmitter biosensing.

Ag and Cu based nanostructures serve as advanced functional materials for biomedical applications, due to their unique properties. Here, we proposed a novel neurotransmitter biosensing method based on Ag-Cu composite nanozyme, synthesized through the soft film plate method. Supported by the soft film template, the Ag-Cu nanozymes were stably kept to an ultrafine 2D structure with high monodispersity, which provided a large specific surface area and sufficient binding sites, leading to controllable and improved dual-nanozyme activities over similar-sized mono-Ag and mono-Cu, and up to 4.95 times of natural enzyme-level. The multi-path enzymatic reaction processes catalyzed by Ag-Cu composite nanozymes were firstly theoretically discussed in detail, according to the theoretical redox potential of redox couples in the reaction systems. On this basis, the Ag-Cu filled nanonets based neurotransmitter biosensing is successfully applied in rapid detection for glutathione and dopamine, possessing a linear range of 10∼100 µM and 1-10 µM, and a detection limit of 3.01 µM and 0.29 µM, respectively, which exhibited superior performance for biomedical purposes over most commercially available products in speed and precision.

Valproic acid increased the efficacy of EGFR TKIs on EGFR/TP53 co-mutated lung cancers and downregulated mutant-p53 levels.

The TP53 tumor suppressor is the most frequently mutated gene in human cancers. For p53-targeted therapy, one of the strategies was targeting mutant p53 for degradation. In EGFR-mutated lung cancer patients, concurrent TP53 mutation was associated with faster resistance to EGFR-TKIs. In this study, we discovered that valproic acid (VPA), a widely prescribed antiseizure medication, had a synergic effect on sensitive as well as acquired resistant lung cancers with EGFR/TP53 co-mutation in combination with EGFR-TKIs. In both in vitro and in vivo models, VPA greatly improved the efficacy of EGFR-TKIs, including forestalling the occurrence of acquired resistance and increasing the sensitivity to EGFR-TKIs. Mechanistically, VPA dramatically promoted degradation of mutant p53 in both sensitive and acquired resistant cells while inhibited mutant TP53 mRNA transcription only in sensitive cells. Together, this study suggested that VPA combination treatment could have beneficial effects on EGFR-mutant lung cancers with concurrent p53 mutation in both early and late stages, expanding the potential clinical applications for VPA.

Metformin Overcomes Acquired Resistance to EGFR TKIs in EGFR-Mutant Lung Cancer via AMPK/ERK/NF-κB Signaling Pathway.

Background: The major limitation of EGFR TKIs in EGFR-mutant lung cancer therapy is the development of acquired resistance. The underlying mechanisms remain unknown in about 30% of cases. NF-κB activation was encountered in the acquired resistance to EGFR TKIs. Unfortunately, none of NF-κB inhibitors has been clinically approved. The most commonly used antidiabetic drug metformin has demonstrated antitumor effects associated with NF-κB inhibition. Therefore, in this study, metformin was examined for its antitumor and antiresistance effects and underlying mechanisms. Methods: In vitro and in vivo EGFR-mutant lung cancer models with acquired resistance to EGFR TKIs were used. Results: We found that NF-κB was activated in EGFR-mutant lung cancer cells with acquired resistance to EGFR TKIs. Metformin inhibited proliferation and promoted apoptosis of lung cancer cells, especially those with acquired EGFR TKI resistance. Moreover, metformin reversed and delayed acquired resistance to EGFR TKIs as well as suppressed cancer stemness in EGFR-mutant lung cancer. Mechanistically, those effects of metformin were associated with activation of AMPK, resulting in the inhibition of downstream ERK/NF-κB signaling. Conclusions: Our data provided novel and further molecular rationale and preclinical data to support combination of metformin with EGFR TKIs to treat EGFR-mutant lung cancer patients, especially those with acquired resistance.

Repositioning Aspirin to Treat Lung and Breast Cancers and Overcome Acquired Resistance to Targeted Therapy.

Background: The major limitation of targeted cancer therapy is development of acquired resistance. Intratumoral heterogeneity and coexist of multiple resistance mechanisms make combination therapies targeting one specific mechanism inefficient. Methods: Transcriptional signature obtained from GEO was used to reposition FDA-approved drugs to treat lung and breast cancers as well as overcome acquired resistance to EGFR TKIs in lung cancer and to tamoxifen in breast cancer via CMap. In vitro and in vivo models were used to examine candidate drugs for their anti-cancer and anti-resistance efficacy and underlying mechanisms. Results: We found that aspirin, the most commonly used drug, not only inhibited proliferation and promoted apoptosis of cancer cells, but also delayed and overcame acquired resistance to targeted therapy using in vitro and in vivo models. The underlying mechanism could be attributed to enhanced cancer stemness and activated NF-κB signaling in acquired resistant tumors, both of which were suppressed by aspirin and rendered resistant tumors more sensitive to aspirin. Conclusions: Our data identify aspirin as a potential candidate for combination therapy for lung and breast cancers.

[Simultaneous determination of five alkaloids in Niuhuang Shangqing Tablets by micellar electrokinetic chromatography-mass spectrometry using laurel acyl malic acid ester].

A micellar electrokinetic chromatography-mass spectrometric method based on laurel acyl malic acid ester (LMAE) for the separation and determination of coptisine, berberine, jatrorrhizine, phellodendrine and ligustrazine in Niuhuang Shangqing Tablets was established. The baseline separation of the five compounds was attained within 18 min by an uncoated capillary (88 cm x 50 microm) on the operating voltage of 25 kV using 7.5 mmol/L LMAE-15 mmol/L ammonia-50 mmol/L ammonium acetate mixture (pH = 7.0) containing 12.5% (v/v) acetonitrile as the electrophoretic medium and 50% 2-propanol aqueous solution (containing 3 mmol/L acetic acid) as the sheath liquid. The peak area of each component to its concentration showed a good linear relationship. The relative standard deviations of migration times and peak areas of the five components were less than 5% and the recoveries were between 96.0% and 105%. The developed method is simple, rapid, accurate and is suitable for the routine analysis of the five alkaloid components in Niuhuang Shangqing Tablets.